gregg w. stone md for the acuity investigators gregg w. stone md for the acuity investigators a...

Gregg W. Stone MD

for the ACUITY Investigators

Gregg W. Stone MD

for the ACUITY Investigators

A Prospective, Randomized Trial of Bivalirudin in Acute Coronary Syndromes

Final One-Year Results from the ACUITY Trial

A Prospective, Randomized Trial of Bivalirudin in Acute Coronary Syndromes

Final One-Year Results from the ACUITY Trial

Moderateand highrisk ACS

(n=13,819)

Study Design – First RandomizationStudy Design – First Randomization

An

gio

gra

ph

y w

ith

in 7

2h

Aspirin in allClopidogrel

dosing and timingper local practice



UFH/Enox+ GP IIb/IIIa(n=4,603)

Bivalirudin+ GP IIb/IIIa(n=4,604)

BivalirudinAlone

(n=4,612)

R*

*Stratified by pre-angiography thienopyridine use or administration*Stratified by pre-angiography thienopyridine use or administration

Moderate and high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819)


Medicalmanagement

PCI

CABG

56%

11%

33%

Study Design – Second RandomizationStudy Design – Second Randomization

UFH/Enox+ GP IIb/IIIa(N=4,603)

Bivalirudin+ GP IIb/IIIa(N=4,604)

BivalirudinAlone

(N=4,612)

R*

GPI upstream (N=2294)

GPI CCL for PCI (N=2309)

GPI upstream (N=2311)

GPI CCL for PCI (N=2293)





*Stratified by pre-angiography thienopyridine use or administration*Stratified by pre-angiography thienopyridine use or administration

Moderateand highrisk ACS(n=13,819



0 30 60 90 120 150 180 210 240 270 300 330 360 3900

5

15

25

Isch

emic

Co

mp

osi

te (

%)

Days from Randomization

10

20 UFH/Enoxaparin + IIb/IIIaBivalirudin + IIb/IIIa

Bivalirudin alone

EstimateP

(log rank)

30 day

7.4%0.367.8%0.347.9%

—

EstimateP

(log rank)

16.3%0.3816.5%0.3116.4%

1 year

—

p=0.55

H+GPI vs. Bivalirudin aloneHR [95% CI] = 1.05 (0.95-1.17)

H+GPI vs. Bivalirudin+GPI HR [95% CI] = 1.05 (0.94-1.16)

Ischemic Composite Endpoint(Death, MI, unplanned revascularization for ischemia)

Ischemic Composite Endpoint(Death, MI, unplanned revascularization for ischemia)

UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin AloneUFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone

Myocardial InfarctionMyocardial Infarction

0 30 60 90 120 150 180 210 240 270 300 330 360 3900

5

10

15



UFH/Enoxaparin + IIb/IIIaBivalirudin + IIb/IIIa

Bivalirudin alone

EstimateP

(log rank)

30 day

4.4%0.694.6%0.364.8%

—

EstimateP

(log rank)

6.2%0.636.4%0.107.1%

1 year

—

p=0.24

MI

(%)

0 30 60 90 120 150 180 210 240 270 300 330 360 3900

5

10

15


Un

pla

nn

ed R

evas

c. (

%)


Bivalirudin alone


Unplanned RevascularizationUnplanned Revascularization

EstimateP

(log rank)

30 day

2.3%0.202.8%0.722.4%

—

EstimateP

(log rank)

8.6%0.179.5%0.528.9%

1 year

—

p=0.39

0 30 60 90 120 150 180 210 240 270 300 330 360 3900

3

4

5

Ste

nt

Th

rom

bo

sis

(%

)


2

1

Stent Thrombosis (Protocol Defn.)Stent Thrombosis (Protocol Defn.)Drug-eluting Stent (DES) vs. Bare Metal Stent(BMS)Drug-eluting Stent (DES) vs. Bare Metal Stent(BMS)

EstimateP

(log rank)

DES (N=4630)0.38

2.2%

1 year

BMS (N=2528) 2.3%

All (N=7158) 2.2%

0 30 60 90 120 150 180 210 240 270 300 330 360 3900

3

4

5

Mo

rtal

ity

(%)


2

1

Mortality: 524 total deaths at 1-yearMortality: 524 total deaths at 1-yearUFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin AloneUFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone


Bivalirudin alone

EstimateP

(log rank)

1.4%0.531.6%0.391.6%

—

EstimateP

(log rank)

4.4%0.934.2%0.663.8%

1 year

—

p=0.90

H+GPI vs. Bivalirudin aloneHR [95% CI] = 0.95 (0.78-1.18)

H+GPI vs. Bivalirudin+GPI HR [95% CI] = 0.99 (0.80-1.21)

0 1 2

Death at 1-YearDeath at 1-YearUFH/Enoxaparin + GPIIb/IIIa vs. Bivalirudin aloneUFH/Enoxaparin + GPIIb/IIIa vs. Bivalirudin alone

Hazard ratio±95% CI

Hazard ratio±95% CI

Bivalalone

UFH/Enox+ IIb/IIIa

HR (95% CI) Pint

0.96

Bivalirudin alone betterBivalirudin alone better UFH/Enox + IIb/IIIa betterUFH/Enox + IIb/IIIa better

3.2% 4.0% 0.95 (0.70-1.29)

6.8% 6.7% 1.03 (0.64-1.66)

4.0% 4.3% 0.95 (0.66-1.37)

Actual Treatment

PCI (n=5179)

CABG (n=1040)

Medical (n=2994)

4.8%

2.4%

5.0%

3.6%

1.04 (0.80-1.34)

0.84 (0.55-1.28)0.40

Biomarkers (CK/Trop)

Elevated (n=5072)

Normal (n=3402)

3.5%

4.0%

4.2%

4.4%

0.90 (0.68-1.18)

1.05 (0.74-1.48)0.52

Pre Thienopyridine

Yes (n=5751)

No (n=3305)

1 yr KM estimate

Mo

rtal

ity

(%)


0 30 60 90 120 150 180 210 240 270 300 330 360 3900

5

15

30

10

25

20

p=0.04

1 yearEstimate

Major Bleed only (without MI) (N=551) 12.5%28.9%Both MI and Major Bleed (N=94)

3.4%No MI or Major Bleed (N=12,557)MI only (without Major Bleed) (N=611) 8.6%

Impact of MI and Major Bleeding (non-CABG) in the First 30 Days on Risk of Death Over 1 Year

Cox model adjusted for baseline predictors, with non-CABG major bleeding and MI as time-updated covariates

Cox model adjusted for baseline predictors, with non-CABG major bleeding and MI as time-updated covariates

Influence of Major Bleeding and MI in the First 30 Days on Risk of Death Over 1 Year

Major bleedingMajor bleeding 2.89 (2.24-3.72)2.89 (2.24-3.72) <0.0001<0.0001

Myocardial InfarctionMyocardial Infarction 2.47 (1.87-3.27)2.47 (1.87-3.27) <0.0001<0.0001

0 1 2 3 4

HR ± 95% CIHR ± 95% CI P-valueP-valueHR (95% CI)HR (95% CI)

ConclusionsConclusions

In patients with moderate and high risk ACS undergoing an early invasive strategy with the use of GP IIb/IIIa inhibitors

Bivalirudin is an acceptable substitute for either unfractionated heparin or enoxaparin

Compared to either UFH/enoxaparin with GP IIb/IIIa inhibitors or bivalirudin with GP IIb/IIIa inhibitors

A bivalirudin alone strategy results in marked reduction of bleeding at 30 days, and similar rates of mortality and composite ischemia at 1-year

The results of this study further establish the important relationship between iatrogenic bleeding complications and the long-term prognosis in patients with ACS

In patients with moderate and high risk ACS undergoing an early invasive strategy with the use of GP IIb/IIIa inhibitors

Bivalirudin is an acceptable substitute for either unfractionated heparin or enoxaparin

Compared to either UFH/enoxaparin with GP IIb/IIIa inhibitors or bivalirudin with GP IIb/IIIa inhibitors

A bivalirudin alone strategy results in marked reduction of bleeding at 30 days, and similar rates of mortality and composite ischemia at 1-year

The results of this study further establish the important relationship between iatrogenic bleeding complications and the long-term prognosis in patients with ACS

gregg w. stone md for the acuity investigators gregg w. stone md for the acuity investigators a...

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